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Flu virus wipes out immune system's first responders to establish infection
Date:10/20/2013

CAMBRIDGE, Mass. (October 20, 2013) -- Revealing influenza's truly insidious nature, Whitehead Institute scientists have discovered that the virus is able to infect its host by first killing off the cells of the immune system that are actually best equipped to neutralize the virus.

Confronted with a harmful virus, the immune system works to generate cells capable of producing antibodies perfectly suited to bind and disarm the hostile invader. These virus-specific B cells proliferate, secreting the antibodies that slow and eventually eradicate the virus. A population of these cells retains the information needed to neutralize the virus and takes up residence in the lung to ward off secondary infection from re-exposure to the virus via inhalation.

On the surface of these so-called memory B cells are high-affinity virus-specific receptors that bind virus particles to reduce viral spread. While such cells should serve at the body's first line of defense, it turns out that flu virus exploits the specificity of the cells' receptors, using them to gain entry, disrupt antibody production, and ultimately kill the cells. By dispatching its enemies in this fashion, the virus is able to replicate efficiently before the immune system can mount a second wave of defense. This seemingly counter-intuitive pathway to infection is described this week in the journal Nature.

"We can now add this to the growing list of ways that the flu virus has to establish infection," says Joseph Ashour, a co-author of the Nature paper and a postdoctoral researcher in the lab of Whitehead Member Hidde Ploegh.

"This is how the virus gains a foothold," adds Ploegh lab postdoc Stephanie Dougan, also a co-author of the study. "The virus targets memory cells in the lung, which allows infection to be established -- even if the immune system has seen this flu before."

Discovering this dynamic of the virus was no small task, in part because vi
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Contact: Matt Fearer
fearer@wi.mit.edu
617-452-4630
Whitehead Institute for Biomedical Research
Source:Eurekalert

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